Detoxification of lipophilic endogenous substrates and noxious foreign compounds often requires a multistep process involving oxidation and conjugation. Monooxygenase activity catalyzes oxygenation of the ubiquitous environmental pollutant, benzo(a)pyrene, such that oxides, quinones, diols, and phenols form. Certain diols which are generally not detoxified through conjugation reactions may be further oxygenated to reactive arene oxides which are potent mutagens and carcinogens. With benzo(a)pyrend as substrate, studies with hepatic tissue from mice indicate that (1) certain phenols can also be further metabolized by the appropriate monooxygenase system to potent mutagens and DNA binding species and (2) substrates for the conjugating enzymes, sulfotransferase(s) and UDP glucuronosyltransferases, can protect against phenol-derived mutagenesis and DNA binding. With bilirubin as substrate, our studies show that two peaks of UDP glucuronosyltransferase activity are induced by certain aromatic compounds in hydrocarbon-responsive C57BL/6N mice and one peak of activity is induced in hydrocarbon-nonresponsive DBA/2N mice. Appropriate genetic crosses show that induction of the 10-day peaks in UDP glucuronosyltransferase is genetically regulated and is associated with the Ah locus. The biochemical characterization and physiological significance of these two transferases are under investigation.